Synthesis, biological evaluation and molecular investigation of fluorinated peroxisome proliferator-activated receptors 伪/纬 dual agonists

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• 作者：Giuseppe Fracchiolla^a ; Antonio Laghezza^a ; Luca Piemontese^a ; Mariagiovanna Parente^a ; Antonio Lavecchia^b ; ^{lavecchi@unina.it} ; Giorgio Pochetti^c ; Roberta Montanari^c ; Carmen Di Giovanni^b ; Giuseppe Carbonara^a ; Paolo Tortorella^a ; Ettore Novellino^b ; Fulvio Loiodice^a ; ^{floiodice@farmchim.uniba.it}
• 关键词：Structure&ndash ; activity relationships ; Carboxylic acids ; Nuclear receptors ; Crystallographic studies ; Docking experiments
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2012
• 期刊代码：9_09680896
• 类别：ch
• 出版时间：15 March, 2012
• 卷：20
• 期：6
• 页码：2141-2151
• 文件大小：1079 K

摘要

PPARs are transcription factors that govern lipid and glucose homeostasis and play a central role in cardiovascular disease, obesity, and diabetes. Thus, there is significant interest in developing new agonists for these receptors. Given that the introduction of fluorine generally has a profound effect on the physical and/or biological properties of the target molecule, we synthesized a series of fluorinated analogs of the previously reported compound 2, some of which turned out to be remarkable PPAR伪 and PPAR纬 dual agonists. Docking experiments were also carried out to gain insight into the interactions of the most active derivatives with both receptors.